title: Clinical presentation and molecular identification of four uncommon alpha globin variants in Thailand. Initiation codon mutation of α2-globin Gene (HBA2:c.1delA), donor splice site mutation of α1-globin gene (IVSI-1, HBA1:c.95 + 1G>A), hemoglobin Queens Park/Chao Pra Ya (HBA1:c.98T>A) and hemoglobin Westmead (HBA2:c.369C>G).
abstract: Alpha thalassemia is the most common genetic disease in the world with the prevalence of carriers ranging from 5-50% in several populations. Coinheritance of two defective α-globin genes usually gives rise to a symptomatic condition, hemoglobin (Hb) H disease. Previously, it has been suggested from several studies in different populations that nondeletional Hb H disease (--/α(T)α or --/αα(T)) is generally more severe than the deletional type (--/-α). In this report, we describe four rare nondeletional α-thalassemia mutations in Thai individuals, including initiation codon mutation (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens Park (HBA1:c.98T>A) [α32(B13)Met>Lys], and Hb Westmead (HBA2:c.369C>G) [α122(H5)His>Gln]. Interactions of the first three mutations with the α(0)-thalassemia resulted in nondeletional Hb H disease; however, their clinical presentations were rather mild and some were detected accidentally. This suggests that a genotype-phenotype correlation of α-thalassemia syndrome might be more heterogeneous and so the type of mutation does not simply imply the prediction of the resulting phenotype. Our data will be of use in future genetic counseling of such conditions that are increasingly identified thanks to the improvement of molecular analysis in routine laboratories.
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Supachai
authors.initials: S
authors.lastname: Ekwattanakit
authors.forename: Nipon
authors.initials: N
authors.lastname: Chalaow
authors.forename: Suchada
authors.initials: S
authors.lastname: Riolueang
authors.forename: Sirirat
authors.initials: S
authors.lastname: Wijit
authors.forename: Porntep
authors.initials: P
authors.lastname: Tanyut
authors.forename: Nunthawut
authors.initials: N
authors.lastname: Chat-Uthai
authors.forename: Kalaya
authors.initials: K
authors.lastname: Tachavanich
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000740:Anemia / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D018387:Codon, Initiator / Q000235:genetics*; D003715:Dengue / Q000097:blood / Q000150:complications; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000209:etiology; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D033162:Incidental Findings; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010322:Parvoviridae Infections / Q000097:blood / Q000150:complications; D016732:Parvovirus B19, Human; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D013163:Splenomegaly / Q000209:etiology; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D006455:Hemoglobins, Abnormal; D022821:RNA Splice Sites; D055542:alpha-Globins; C550545:hemoglobin Queens Park; C056329:Hemoglobin Westmead; C030448:hemoglobin Bart's